Knockout of RNA Binding Protein MSI2 Impairs Follicle Development in the Mouse Ovary: Characterization of MSI1 and MSI2 during Folliculogenesis.

Characterizing the mechanisms underlying follicle development in the ovary is crucial to understanding female fertility and is an area of increasing research interest. The RNA binding protein Musashi is essential for post-transcriptional regulation of oocyte maturation in Xenopus and is expressed during ovarian development in Drosophila. In mammals Musashi is important for spermatogenesis and male fertility, but its role in the ovary has yet to be characterized. In this study we determined the expression of mammalian Musashi proteins MSI1 and MSI2 during mouse folliculogenesis, and through the use of a MSI2-specific knockout mouse model we identified that MSI2 is essential for normal follicle development. Time-course characterization of MSI1 and MSI2 revealed distinct differences in steady-state mRNA levels and protein expression/localization at important developmental time-points during folliculogenesis. Using a gene-trap mouse model that inactivates Msi2, we observed a significant decrease in ovarian mass, and change in follicle-stage composition due to developmental blocking of antral stage follicles and pre-antral follicle loss through atresia. We also confirmed that hormonally stimulated Msi2-deficient mice produce significantly fewer MII oocytes (60.9% less than controls, p < 0.05). Furthermore, the majority of these oocytes are of poor viability (62.2% non-viable/apoptotic, p < 0.05), which causes a reduction in female fertility evidenced by decreased litter size in Msi2-deficient animals (33.1% reduction to controls, p < 0.05). Our findings indicate that MSI1 and MSI2 display distinct expression profiles during mammalian folliculogenesis and that MSI2 is required for pre-antral follicle development.

Translational control in germ cell development: A role for the RNA-binding proteins Musashi-1 and Musashi-2.

Mammalian gametogenesis is a complex process involving specialised cell cycle progression and differentiation. As part of their differentiation, germ cells experience periods of transcriptional inactivation and chromatin inaccessibility whilst continuing to coordinate the correct temporal and spatial expression of genes required for continued development. To overcome these obstacles, mammalian germ cells express a wide variety of sequence-specific RNA-binding proteins, which assist in the translational control of many mRNA transcripts which are produced and stored during periods of high mRNA synthesis. In this review we focus on the Musashi family of RNA-binding proteins, a highly conserved family of translational regulatory proteins whose recent identification in germ cells of Drosophila and Xenopus, as well as their well described role in processes such as cell cycle progression and stem cell identity, has led us to investigate the role of these proteins in mammalian germ cell development.